Rustichelli Serena, Lanni Cristina, Zarà Marta, Guidetti Gianni Francesco, Torti Mauro, Canobbio Ilaria
University School for Advanced Studies (IUSS), 27100 Pavia, Italy.
Department of Biology and Biotechnology, University of Pavia, 27100 Pavia, Italy.
Nutrients. 2024 Dec 23;16(24):4419. doi: 10.3390/nu16244419.
BACKGROUND/OBJECTIVES: Amyloid peptides, whose accumulation in the brain as senile plaques is associated with the onset of Alzheimer's disease, are also found in cerebral vessels and in circulation. In the bloodstream, amyloid peptides promote platelet adhesion, activation, oxidative stress, and thrombosis, contributing to the cardiovascular complications observed in Alzheimer's disease patients. Natural compounds, such as curcumin, are known to modulate platelet activation induced by the hemostatic stimuli thrombin and convulxin. In this study, we investigated the ability of curcumin to modulate platelet activation triggered by amyloid peptides, and we compared its effects with those displayed on platelet activation induced by physiological agonists.
Commercial ultrapure curcumin was used, and platelet aggregation, granule secretion, phosphorylation of selected signaling proteins, and reactive oxygen species production were analyzed on isolated human platelets.
Our results demonstrate that curcumin effectively suppressed platelet aggregation induced by fibrillar amyloid peptides. This effect was associated with the reduction in intracellular signaling pathways involving PKC, PI3K, and MAPK. By contrast, platelet aggregation and activation induced by thrombin and convulxin were only partially reduced by preincubation with curcumin. Moreover, curcumin completely suppressed granule secretion only when platelets were stimulated with hemostatic agonists, but it had no effects upon stimulation with amyloid peptides. Additionally, curcumin reduced the production of reactive oxygen species induced by amyloid peptides with a stronger efficiency compared to platelets stimulated with thrombin.
These results indicate that curcumin displays selective and potent inhibitory activity on platelet responses to pathological stimuli, such as fibrillar amyloid peptides.
背景/目的：淀粉样肽在大脑中以老年斑形式积累与阿尔茨海默病的发病有关，在脑血管和血液循环中也有发现。在血液中，淀粉样肽会促进血小板黏附、激活、氧化应激和血栓形成，导致阿尔茨海默病患者出现心血管并发症。已知姜黄素等天然化合物可调节由凝血刺激物凝血酶和芋螺毒素诱导的血小板激活。在本研究中，我们研究了姜黄素调节淀粉样肽触发的血小板激活的能力，并将其效果与生理激动剂诱导的血小板激活的效果进行了比较。
使用市售超纯姜黄素，对分离出的人血小板分析血小板聚集、颗粒分泌、选定信号蛋白的磷酸化以及活性氧的产生。
我们的结果表明，姜黄素能有效抑制纤维状淀粉样肽诱导的血小板聚集。这种作用与涉及蛋白激酶C（PKC）、磷脂酰肌醇-3激酶（PI3K）和丝裂原活化蛋白激酶（MAPK）的细胞内信号通路的减少有关。相比之下，凝血酶和芋螺毒素诱导的血小板聚集和激活仅在与姜黄素预孵育后部分降低。此外，姜黄素仅在血小板受到凝血刺激物刺激时才完全抑制颗粒分泌，但对淀粉样肽刺激无影响。此外，与凝血酶刺激的血小板相比，姜黄素能更有效地降低淀粉样肽诱导的活性氧的产生。
这些结果表明，姜黄素对血小板对病理性刺激（如纤维状淀粉样肽）的反应具有选择性和强效抑制活性。
